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Discerning the ancestry of European Americans in genetic association studies.

Price AL, Butler J, Patterson N, Capelli C, Pascali VL, Scarnicci F, Ruiz-Linares A, Groop L, Saetta AA, Korkolopoulou P, Seligsohn U, Waliszewska A, Schirmer C, Ardlie K, Ramos A, Nemesh J, Arbeitman L, Goldstein DB, Reich D, Hirschhorn JN - PLoS Genet. (2007)

Bottom Line: Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries.Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure.Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. aprice@broad.mit.edu

ABSTRACT
European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

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The Top Two Axes of Variation of a Dataset of Diverse European SamplesResults are based on (A) 583 markers putatively ancestry-informative markers, and (B) 300 validated markers.
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pgen-0030236-g003: The Top Two Axes of Variation of a Dataset of Diverse European SamplesResults are based on (A) 583 markers putatively ancestry-informative markers, and (B) 300 validated markers.

Mentions: To assess the informativeness of the initial 583 markers for within-Europe ancestry, we genotyped each marker in up to 667 samples from 7 countries: 180 Swedish, 82 UK, 60 Polish, 60 Spanish, 124 Italian, 80 Greek and 81 U.S. Ashkenazi Jewish samples (see Methods). We applied principal components analysis to this dataset using the EIGENSOFT package [11]. Results are displayed in Figure 3A, which clearly separates the same three clusters, roughly corresponding to northwest European, southeast European and Ashkenazi Jewish ancestry, as in our analysis of genome-wide datasets (Figure 2). We note that Spain occupies an intermediate position between northwest and southeast Europe, while Poland lies close to Sweden and UK, supporting a recent suggestion that the northwest-southeast axis could alternatively be interpreted as a north-southeast axis [8].


Discerning the ancestry of European Americans in genetic association studies.

Price AL, Butler J, Patterson N, Capelli C, Pascali VL, Scarnicci F, Ruiz-Linares A, Groop L, Saetta AA, Korkolopoulou P, Seligsohn U, Waliszewska A, Schirmer C, Ardlie K, Ramos A, Nemesh J, Arbeitman L, Goldstein DB, Reich D, Hirschhorn JN - PLoS Genet. (2007)

The Top Two Axes of Variation of a Dataset of Diverse European SamplesResults are based on (A) 583 markers putatively ancestry-informative markers, and (B) 300 validated markers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211542&req=5

pgen-0030236-g003: The Top Two Axes of Variation of a Dataset of Diverse European SamplesResults are based on (A) 583 markers putatively ancestry-informative markers, and (B) 300 validated markers.
Mentions: To assess the informativeness of the initial 583 markers for within-Europe ancestry, we genotyped each marker in up to 667 samples from 7 countries: 180 Swedish, 82 UK, 60 Polish, 60 Spanish, 124 Italian, 80 Greek and 81 U.S. Ashkenazi Jewish samples (see Methods). We applied principal components analysis to this dataset using the EIGENSOFT package [11]. Results are displayed in Figure 3A, which clearly separates the same three clusters, roughly corresponding to northwest European, southeast European and Ashkenazi Jewish ancestry, as in our analysis of genome-wide datasets (Figure 2). We note that Spain occupies an intermediate position between northwest and southeast Europe, while Poland lies close to Sweden and UK, supporting a recent suggestion that the northwest-southeast axis could alternatively be interpreted as a north-southeast axis [8].

Bottom Line: Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries.Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure.Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. aprice@broad.mit.edu

ABSTRACT
European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false-positive or false-negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European, and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

Show MeSH